Motor impulsivity and delay intolerance are elicited in a dose-dependent manner with a dopaminergic agonist in parkinsonian rats
Haritz Jiménez-Urbieta, Belén Gago, Ana Quiroga-Varela, Tatiana Rodríguez-Chinchilla, Leyre Merino-Galán, Manuel Delgado-Alvarado, Irene Navalpotro-Gómez, Arantzazu Belloso-Iguerategui, Concepció Marin, María C Rodríguez-Oroz
Rationale: Impulse control disorders (ICD) and other impulsive-compulsive behaviours are frequently found in Parkinson's disease (PD) patients treated with dopaminergic agonists. To date, there are no available animal models to investigate their pathophysiology and determine whether they can be elicited by varying doses of dopaminergic drugs. In addition, there is some controversy regarding the predispositional pattern of striatal dopaminergic depletion.
Objectives: To study the effect of two doses of pramipexole (PPX) on motor impulsivity, delay intolerance and compulsive-like behaviour.
Methods: Male rats with mild dopaminergic denervation in the dorsolateral striatum (bilateral injections of 6-hydroxidopamine (6-OHDA)) treated with two doses of PPX (0.25 mg/kg and 3 mg/kg) and tested in the variable delay-to-signal paradigm.
Results: Partial (50%) dopaminergic depletion did not induce significant changes in motor impulsivity or delay intolerance. However, 0.25 mg/kg of PPX increased motor impulsivity, while 3 mg/kg of PPX increased both motor impulsivity and delay intolerance. These effects were independent of the drug's antiparkinsonian effects. Importantly, impulsivity scores before and after dopaminergic lesion were positively associated with the impulsivity observed after administering 3 mg/kg of PPX. No compulsive-like behaviour was induced by PPX administration.
Conclusions: We described a rat model, with a moderate dorsolateral dopaminergic lesion resembling that suffered by patients with early PD, that develops different types of impulsivity in a dose-dependent manner dissociated from motor benefits when treated with PPX. This model recapitulates key features of abnormal impulsivity in PD and may be useful for deepening our understanding of the pathophysiology of ICD.
CITATION Psychopharmacology (Berl). 2020 Aug;237(8):2419-2431. doi: 10.1007/s00213-020-05544-6. Epub 2020 May 22.